The 32-story-tall, two-stage Space Launch System (SLS) rocket and its Orion crew capsule were due for blast-off from the Kennedy Space Center in Cape Canaveral, Florida, during a two-hour launch window on Monday morning.
But hopes of a liftoff dimmed as engineers examined an apparent crack in thermal protection material within the core stage, and were trouble-shooting an issue with one of the four engines.
The program, named for the goddess who was Apollo's twin sister in ancient Greek mythology, aims to return astronauts to the moon as early as 2025.
It also seeks to establish a long-term lunar colony as a stepping stone to even more ambitious future voyages sending humans to Mars.
The maiden voyage of the SLS-Orion, a mission dubbed Artemis I, is intended to put the space vehicle through its paces and push design limits before the NASA deems it reliable to carry astronauts.
Billed as the most powerful, complex rocket in the world, the SLS represents the biggest new vertical launch system the US space agency has built since the Saturn V flown during the Apollo moon program of the 1960s and 70s.
One issue cited by NASA officials as a potential show stopper for Monday's launch would be any sign during fueling that a newly repaired hydrogen line fitting had failed to hold. NASA officials said they were also eyeing a potential, but minor, helium leak in launch pad equipment.
Early on Monday morning engineers struggled to configure one of the rocket's four engines for launch and examined a buildup of frost detected on an inner tank seal, according to NASA.
Engineers suspected the frost was from a potential crack in one of the joints connecting the rocket's fuel tanks, NASA said, but that issue was resolved after determining the crack was on foam insulation and not the joint structure.
If the countdown clock is halted, NASA has set September 2 and 5 as backup launch dates.
About 90 minutes after launch, the rocket's upper stage will thrust Orion out of Earth orbit on course for a 42-day flight that brings it to within 96km of the lunar surface before sailing 64,374km beyond the moon and back to Earth. The capsule is expected to splash down in the Pacific on October 10.
Orion will be carrying a simulated crew of three mannequins fitted with sensors to measure radiation levels and other stresses that astronauts would experience.
A top objective for the mission is testing the durability of Orion's heat shield during re-entry as it hits Earth's atmosphere at 39,429km per hour, or 32 times the speed of sound, on its return from lunar orbit - much faster than more common re-entries of astronaut capsules returning from low-Earth orbit.
The heat shield is designed to withstand re-entry friction expected to raise temperatures outside the capsule to nearly 2760 Celsius.
Twelve astronauts walked on the moon during six Apollo missions that landed from 1969 to 1972.
If successful, Artemis I will pave the way to a first crewed SLS-Orion mission, an out-and-back flight around the moon designated Artemis II, as early as 2024, to be followed a year or more later by an Artemis III journey to the lunar surface.
Artemis III involves a much higher degree or complexity integrating the SLS-Orion with a series of spacecraft to be built and flown by Elon Musk's launch company SpaceX.
Those include SpaceX's own heavy-duty Starship launch and lunar-landing vehicle, still under development, as well as several components that remain to be constructed - an orbital fuel depot and space tankers to fill it. Even the new moon-walking suits remain to be designed.
